Notes

Bruton's tyrosine kinase is a prospective restorative focus on inside prostate type of cancer.
Air pollution is a major, global public health concern. A growing body of evidence shows that exposure to air pollutants may impair the brain. Living in highly polluted areas has been linked to several neurodegenerative diseases, where exposure to complex mixtures of air pollutants in urban environments may have harmful effects on brain function. These harmful effects are thought to originate from elevated inflammation and oxidative stress. The olfactory epithelium is a key entry site of air pollutants into the brain as the particles are deposited in the upper airways and the nasal region. A potential source of patient-derived cells for study of air pollutant effects is the olfactory mucosa, which constitutes a central part of the olfactory epithelium. This review first summarizes the current literature on the available in vitro models of the olfactory epithelium. It then describes how alterations of the olfactory mucosa are linked to neurodegeneration and discusses potential therapeutic applications of these cells for neurodegenerative diseases. Finally, it reviews the research performed on the effects of air pollutant exposure in cells of the olfactory epithelium. Patient-derived olfactory epithelial models hold great promise for not only elucidating the molecular and cellular pathophysiology of neurodegenerative disorders, but for providing key understanding about air pollutant particle entry and effects at this key brain entry site. Increasing evidences support that glial connexins are involved in the demyelination pathology of multiple sclerosis (MS), a chronic inflammatory demyelinating disorder. TAK-242 manufacturer Here, we review the data from patients with MS and animal models of MS that implicate connexins in demyelination. Connexins expressed in oligodendrocytes and astrocytes show diverse changes at the different phases of MS. Loss of oligodendrocyte or astrocyte connexins contributes to demyelination and exaggerates the pathology of MS. Channel-dependent and -independent connexins are involved in the pathology of demyelination, which is related with myelin integrity, metabolic homeostasis, the brain-blood barrier, the immune cell infiltration, and the inflammatory response. A comprehensive understanding of connexin function in demyelination may provide new therapeutic targets for MS. AIMS Nanoparticles (NPs) exposure is associated with increased risk of cardiovascular diseases, but the underlying mechanism is still obscure. In this study, we investigated the role of NADPH oxidase 4 (NOX4) in copper oxide nanoparticles (CuONPs)-induced cytotoxicity in human umbilical vein endothelial cells (HUVECs). MATERIALS AND METHODS Morphology changes were examined under the microscope. Cell viability was determined by MTS assay and Calcein AM assay. Apoptosis and the levels of superoxide anion (O2-) and hydrogen peroxide (H2O2) were measured by fluorescence activated cell sorting (FACS). Oxidative stress was detected by assaying the levels of glutathione/glutathione disulfide (GSH/GSSG) and malondialdehyde (MDA). Protein expression levels were determined by western blotting. KEY FINDINGS We revealed that O2- rather than H2O2 was the major component of ROS in CuONPs-treated HUVECs. Meanwhile, CuONPs downregulated expression of O2--eliminating enzyme NOX4 both at mRNA and protein levels, but did not affect the expression of SOD2 and catalase. NOX4 knockdown caused more accumulation of O2-, and a further decrease of H2O2 in CuONPs-treated HUVECs, suggesting that NOX4 regulates the conversion of O2- to H2O2 in CuONPs-treated HUVECs. Furthermore, we revealed that NOX4 knockdown aggravated CuONPs-induced oxidative stress, characterized by a decrease of GSH/GSSG ratio, an increase of MDA level, and upregulation of HSPA5 and γH2AX. Finally, we showed that NOX4 knockdown exacerbated CuONPs-induced apoptotic cell death in HUVECs, indicating that NOX4 could protect ECs from CuONPs-induced cell death. SIGNIFICANCE Our study provides the evidence that NOX4 protects vascular endothelial cells from CuONPs-induced oxidative stress and cell death. Individuals suffering from diabetes have an increased risk of developing cardiovascular complications such as heart failure. Heart failure can be a result of the stiffening of the left ventricle, which occurs when cardiac fibroblasts become "active" and begin to remodel the extracellular matrix (ECM). Fibroblast "activation" can be triggered by the AGE/RAGE signaling cascade. Advanced Glycation End products (AGEs) are produced and accumulate in the ECM over time in a healthy individual, but under hyperglycemic conditions, this process is accelerated. In this study, we investigated how the presence of AGEs in either non-diabetic or diabetic ECM affected fibroblast-mediated matrix remodeling. In order to address this question, diabetic and non-diabetic fibroblasts were embedded in 3D matrices composed of collagen isolated from either non-diabetic or diabetic mice. Fibroblast function was assessed using gel contraction, migration, and protein expression. Non-diabetic fibroblasts displayed similar gel contraction to diabetic cells when embedded in diabetic collagen. Thus, suggesting the diabetic ECM can alter fibroblast function from an "inactive" to "active" state. Addition of AGEs increase the AGE/RAGE cascade leading to increased gel contraction, whereas inhibiting the cascade resulted in little or no gel contraction. These results indicated 1) the ECM from diabetic and non-diabetic mice differ from one another, 2) diabetic ECM can impact fibroblast function and shift them toward an "active" state, and 3) that fibroblasts can modify the ECM through activation of the AGE/RAGE signaling cascade. These results suggested the importance of understanding the impact diabetes has on the ECM and fibroblast function. AIMS Liver fibrosis is a chronic liver disease characterized by hepatic stellate cell (HSC) activation. Peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in HSC activation. This study aimed to investigate the role of PPARγ in the progression of human hepatic fibrosis and the mechanism by which microRNA-942 regulates HSC activation. METHODS 70 chronic hepatitis B (CHB) patients liver tissues were used to assess PPARγ, α-SMA and miR-942 levels by immunoblot and real-time PCR. Human primary HSCs or LX2 cells were used to perform multiple molecular experiments based on the transfection of small interfering RNA (siRNA) or co-transfection of microRNA inhibitor. Site-directed mutagenesis and luciferase reporter assays were used to identify miR-942 targets. miR-942 expression and localization in hepatic fibrosis and co-localization between α-SMA were determined by fluorescence in situ hybridization (FISH). KEY FINDINGS The mRNA expression of PPARγ was decreased in activated HSCs and patients with liver fibrosis, which negatively correlated with F stage and α-SMA.
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